NCT00049322已完成2 期
A Phase II Study Of rhuMAb VEGF (BEVACIZUMAB) In Patients With Hepatocellular Carcinoma Receiving Chemoembolization
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Neovessel Formation as Measured by Angiogram at 14 Weeks
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as liposomal doxorubicin, cisplatin, and mitomycin, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. Chemoembolization kills tumor cells by blocking the blood flow to the tumor and keeping chemotherapy drugs near the tumor. Monoclonal antibodies, such as bevacizumab, can kill any tumor cells that are left after chemoembolization by blocking their ability to grow and spread.
PURPOSE: This randomized phase II trial is studying to see if chemoembolization followed by bevacizumab works better than chemoembolization alone in treating patients who have liver cancer that cannot be removed with surgery.
详细描述
OBJECTIVES:
- Compare neovessel formation at 8 and 14 weeks after hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma treated with bevacizumab versus no bevacizumab (observation after chemoembolization only).
- Compare time to progression, objective response rate, and tumor marker progression in patients treated with these regimens.
- Determine the pharmacokinetics of bevacizumab in patients with liver function impairment.
- Determine the toxic effects of this drug in these patients.
- Compare the cancer biomarker pattern of peripheral blood cells and plasma before and after chemoembolization in patients treated with these regimens.
OUTLINE: This is a randomized, open-label study.
All patients receive hepatic artery chemotherapy (chemoembolization) comprising doxorubicin HCl liposome, cisplatin, and mitomycin on day 8 and possibly on day 92. Patients are then randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes once every 2 weeks beginning 1 week prior to the first chemoembolization. Courses repeat every 2 weeks in the absence of disease progression or unacceptable toxicity.
- Arm II: Patients do not receive bevacizumab. Patients in arm II may cross-over receive bevacizumab as in arm I if recurrent tumor is evident at week 14 by CT scan or MRI or a 50% or greater increase in AFP level has occurred since day 8 chemoembolization.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 year old
- •Histologically or cytologically documented HCC
- •Patients must have bi-dimensional measurable disease by CT or MRI scan that does not exceed 50% of the liver parenchyma
- •Patients must be considered clinical candidates for chemoembolization, with at least one lesion > 3cm and no lesion > 15cm in its longest diameter
- •Patients awaiting cadaveric orthotopic liver transplantation are eligible if they meet all other criteria. These patients must have a model for end-stage liver disease priority score < 28 points at entry
- •Cirrhosis Child-Pugh class A or B
- •Patients with documented grad III varices or prior history of UGI bleeding will require endoscopic evaluation prior to treatment under this protocol.
- •Platelet count equal or greater than 60,000/μL
- •Female patients must use effective contraception, be surgically sterile or be postmenopausal; male patients must be using barrier contraception or be surgically sterile
- •Patients must be willing and able to comply with all study requirements and have signed the informed consent
排除标准
- •Previous history of liver transplantation
- •Fibrolamellar histology
- •Prior antiangiogenesis therapy
- •Presence of extrahepatic disease
- •Presence of biliary obstruction defined as biliary dilatation and total bilirubin > 2.5mg/dl
- •Thrombosis of the main portal vein
- •Absolute contraindications to doxorubicin, mitomycin-C, cisplatin, iodinated contrast material, Avitene or dexamethasone treatment
- •Other active malignancies during the past year (except for non-melanoma skin cancer or in situ carcinomas)
- •ECOG PS> 2 or life expectancy < 12 weeks
- •History or evidence upon physical examination of CNS disease
- •Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to Day 0, or anticipation of need for major surgical procedure within 3 months of study entry; fine needle aspirations within 7 days prior to Day 0
- •Current or recent (within the 10 days prior to Day 0) use of full-dose oral or parenteral anticoagulants (except as required to maintain patency of preexisting, permanent indwelling IV catheters) or thrombolytic agent (for subjects receiving warfarin, international normalized ration of < 1.5)
- •Chronic, daily treatment with aspirin (> 325mg/day) or nonsteroidal anti-inflammatory medications
- •Positive pregnancy test or lactation
- •Proteinuria at baseline or clinically significant impairment of renal function. Subjects unexpectedly discovered to have > 1+ proteinuria at baseline should undergo a 24-hour urine collection, which must be an adequate collection and must demonstrate < 500 mg of protein/24 hr to allow participation in the study
- •Serious, nonhealing wound, ulcer, or bone fracture
- •Evidence of bleeding diathesis or coagulopathy
- •Current or recent (within the 28 days prior to Day 0) participation in another experimental drug study
- •Clinically significant cardiovascular disease, New York Heart Association Grade II or greater congestive heart failure, serious cardiac arrhythmia requiring medication, or Grade II or greater peripheral vascular disease within 1 year prior to Day 0
- •Prior history of hypertensive crisis of hypertensive encephalopathy
- •History of abdominal fistula or gastrointestinal perforation within 6 months prior to Day 1
- •History of hemoptysis within 1 month prior to Day 1
- •Significant vascular disease within 6 months prior to Day 1
- •Screening clinical laboratory values:
- •ANC of < 1500/μL
- •INR of > 1.5
- •Total bilirubin of > 2.5mg/dL
- •AST or ALT > 5 times upper limit of normal
- •Serum creatinine of > 2.0 mg/dL or creatinine clearance < 45 mL/min
- •Hemoglobin of < 8.5 gm/dL
- •History of other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the subject at high risk from treatment complications
结局指标
主要结局
Neovessel Formation as Measured by Angiogram at 14 Weeks
时间窗: 14 weeks
Angiograms were assessed for changes in vascularity. The numbers indicate how many subjects in each group showed neovessel formation.
次要结局
- Assess the Toxicities of Bevacizumab in Patients With Liver Function Impairment(16 weeks)
- Progression Free Survival(16 weeks)
- Measure (Vascular Endothelial Growth Factor)VEGF Before and After TACE With and Without Bevacizumab(21 days after TACE)
- Assess Pharmakokinetics of Bevacizumab in Liver Disease(day 85)
研究者
研究点 (2)
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